In recent years, a better understanding of protein interaction networks has led to the identification of highly connected hub proteins and pathways that are commonly used by a number of different pathogens and in a range of diseases. These hubs represent promising targets for drug development as depicted in FIG. 1A.
Most disease networks have the “small-world” property, where proteins are only a few interactions away from any other proteins. Therefore, inhibiting a given node can potentially affect the state of most nodes in its vicinity as well as the activity of the network itself. In this way, therapeutic inhibition of nodes and hubs within one disease network can affect other disease modules or pathways.
Cytotoxic bacterial and plant toxins have evolved to exploit host proteins and cellular pathways that mediate the entry of those toxins into host cells and to induce cell-death. Although toxins exploit unique host pathways, these pathways are interconnected. For example, while anthrax, diphtheria, and Botulinum toxins reach the cytoplasm from acidified endosomes, cholera, Pseudomonas aeruginosa and ricin toxins are transported into the cytoplasm through the host ER-associated degradation pathway. These pathways interconnect at host “hub” proteins. It is known that multiple infectious pathogens or toxins that negatively affect hosts by different mechanisms exploit the same host pathways. Accordingly, it is feasible for multiplex approaches to lead to the discovery of a therapy for broadly active and host-oriented infectious diseases that target the host function being exploited by multiple pathogenic agents.